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Application of Chitosan Chitooligosaccharide and Their Derivatives in the Treatment of Alzheimer’s Disease

机译:壳聚糖壳寡糖及其衍生物在阿尔茨海默氏病治疗中的应用

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摘要

Classic hypotheses of Alzheimer’s disease (AD) include cholinergic neuron death, acetylcholine (ACh) deficiency, metal ion dynamic equilibrium disorder, and deposition of amyloid and tau. Increased evidence suggests neuroinflammation and oxidative stress may cause AD. However, none of these factors induces AD independently, but they are all associated with the formation of Aβ and tau proteins. Current clinical treatments based on ACh deficiency can only temporarily relieve symptoms, accompanied with many side-effects. Hence, searching for natural neuroprotective agents, which can significantly improve the major symptoms and reverse disease progress, have received great attention. Currently, several bioactive marine products have shown neuroprotective activities, immunomodulatory and anti-inflammatory effects with low toxicity and mild side effects in laboratory studies. Recently, chitosan (CTS), chitooligosaccharide (COS) and their derivatives from exoskeletons of crustaceans and cell walls of fungi have shown neuroprotective and antioxidative effects, matrix metalloproteinase inhibition, anti-HIV and anti-inflammatory properties. With regards to the hypotheses of AD, the neuroprotective effect of CTS, COS, and their derivatives on AD-like changes in several models have been reported. CTS and COS exert beneficial effects on cognitive impairments via inhibiting oxidative stress and neuroinflammation. They are also a new type of non-toxic β-secretase and AChE inhibitor. As neuroprotective agents, they could reduce the cell membrane damage caused by copper ions and decrease the content of reactive oxygen species. This review will focus on their anti-neuroinflammation, antioxidants and their inhibition of β-amyloid, acetylcholinesterase and copper ions adsorption. Finally, the limitations and future work will be discussed.
机译:阿尔茨海默氏病(AD)的经典假设包括胆碱能神经元死亡,乙酰胆碱(ACh)缺乏,金属离子动态平衡障碍以及淀粉样蛋白和tau蛋白沉积。越来越多的证据表明神经炎症和氧化应激可能引起AD。但是,这些因素均未独立诱导AD,但它们均与Aβ和tau蛋白的形成有关。目前基于ACh缺乏症的临床治疗只能暂时缓解症状,并伴有许多副作用。因此,寻找可以显着改善主要症状并逆转疾病进展的天然神经保护剂受到了极大的关注。当前,几种生物活性海产品在实验室研究中显示出神经保护活性,免疫调节和抗炎作用,且毒性低,副作用轻。最近,壳聚糖(CTS),壳寡糖(COS)及其来自甲壳类外骨骼和真菌细胞壁的衍生物已显示出神经保护和抗氧化作用,基质金属蛋白酶抑制作用,抗HIV和抗炎特性。关于AD的假设,已经报道了CTS,COS及其衍生物对几种模型中AD样变化的神经保护作用。 CTS和COS通过抑制氧化应激和神经炎症对认知障碍发挥有益作用。它们还是新型的无毒β-分泌酶和AChE抑制剂。作为神经保护剂,它们可以减少铜离子引起的细胞膜损伤,并减少活性氧的含量。这篇综述将集中于它们的抗神经炎症,抗氧化剂及其对β-淀粉样蛋白,乙酰胆碱酯酶和铜离子吸附的抑制作用。最后,将讨论局限性和未来的工作。

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